Localization of radiolabeled monoclonal antibodies in thyroid tumor xenografts.

Monoclonal antibodies to human thyroglobulin were produced using the hybridoma technique. Two monoclonal antibodies D5I and F9I were radiolabeled with 125I and used for radioimmunolocalization studies in an immunosuppressed animal model bearing xenografts of human thyroid tumor tissue. Biodistribution studies were carried out at various time intervals post-injection. Maximum tumor uptake was obtained at 72 hr after administration of the antibodies. The absolute tumor uptake (ATU) expressed as percentage of injected dose per gram of tissue (% ID/g) was 15.49 +/- 2.47, 4.51 +/- 0.69 and 2.50 +/- 0.41 for D5I, F9I and control Igs respectively. The tumor to blood ratios (T/B) obtained were 3.01 +/- 0.43 for D5I, 0.98+/-0.2 for F9I and 0.47 +/- 0.12 for control Igs. ATU as well as T/B ratio obtained with D5I was significantly higher as compared to F9I and control Igs. The results indicated the potential application of radiolabeled monoclonal antibodies to human thyroglobulin for tumor targetting in patients of differentiated thyroid carcinoma, particularly those metastases which did not concentrate radioiodine.

Left sided cervical and thoracic malignant extra-adrenal pheochromocytoma.

Extra-adrenal Pheochromocytomas are rare entities. High index of suspicion among diastolic hypertensives followed by screening test for 24-hour urinary catecholamine level helps in diagnosis. 123I MIBG scintigraphy is specific for tumour localisation and surgical debulking of tumour or 131I MIBG therapy are alternative modes of treatment.

Targetted localisation and imaging of a murine lymphoma using 131I-labelled monoclonal antibody.

In vivo tumor targetting with radiolabelled monoclonal antibodies is a promising approach for the diagnosis and therapy of tumors. A specific monoclonal antibody (mAb), DLAB was generated to the Dalton's lymphoma associated antigen (DLAA) from Haemophilus paragallinarum-induced spontaneous fusion. In order to study the tumor localisation and biodistribution properties of the monoclonal antibody, scintigraphic studies were performed using the radiolabelled DLAB. 131-labelled DLAB was administered intravenously into Swiss mice bearing Dalton's lymphoma and external scintiscanning was performed at different time intervals. Clear tumor images were obtained which revealed selective and specific uptake of radiolabel and the results were compared with biodistribution data. The radioiodinated monoclonal antibody showed fast tumor uptake which increased significantly to 14.6% injected dose (ID)/g at 12 hr post-injection. Enhanced blood clearance of radioactivity resulted in higher tumor/blood ratio of 5.96 at 48 hr. 131I-labelled DLAB resulted in selective and enhanced uptake of the radioactivity by the tumor compared to the non-specific antibody and the results suggest the potential use of spontaneous fusion for producing specific monoclonal antibodies for tumor detection and therapy.

Discordant findings of Iodine-131 scintiscan and chest radiogram in carcinoma of thyroid patients.

Since 1987, 560 patients have been treated in our department for carcinoma of thyroid with radioactive Iodine-131. Recently, we have come across a patient with bilateral pulmonary concentration of Iodine-131, that is visualised on Iodine-131 whole body scintiscan, whereas chest radiogram was negative. Respectively, the files of 560 patients of carcinoma of thyroid were analysed. It is found, out of 560 patients treated, 16 patients, had pulmonary concentration of Iodine-131. The chest radiogram was normal in six out of these 16 patients. Details of both chest radiogram and scintiscans are presented in this study.

Solitary thyroid nodule: a study of 100 cases.

One hundred cases of solitary thyroid nodules attending the thyroid clinic, Institute of Postgraduate Medicine & Research, Dhaka (IPGMR) and the Institute of Nuclear Medicine (INM) were included in a prospective study. Thyroid ultrasonography (USG), scintiscanning, radioactive iodine (I131) uptake (RAIU), estimation of serum total T3, T4 & TSH and Fine Needle Aspiration Cytology (FNAC) were performed in all cases. Surgical resection with histopathologic study was performed in selected cases. Extra-nodular part of the thyroid gland was normal in 68 and diffusely enlarged in 32, RAIU was normal in 62, high in 36 and very low in two subjects. Nodules were solid at USG in 67 subjects, cystic in 16 subjects and of mixed consistency in 17 subjects. Goitrous subjects had significantly lower T4 (p < 0.001) and higher T3 (p < 0.01) and TSH (p < 0.001) than non-goitrous ones. Colloid nodule was the commonest pathology occurring in 41 cases, followed by thyroid cysts (26), follicular adenoma (23), adenoma with cystic change (7), subacute thyroiditis (2) and papillary carcinoma (1). Colloid nodules were more common in goitrous subjects which could hint at iodine deficiency as the major cause of such nodules. Hyperfunctioning follicular adenomas occurred exclusively in non-goitrous subjects. Carcinoma appeared to be uncommon in patients with solitary nodules. It gives an opportunity to our physicians to be more conservative in selecting patients with solitary thyroid nodules for surgical treatment.

131I-MIBG scintigraphy in neural crest tumours.

Radioiodinated meta-iodobenzylguanidine (131I-MIBG) has been widely used for the diagnosis of neuroblastomas, pheochromocytomas, paragangliomas and medullary carcinomas of thyroid. We have developed a procedure for preparation of 131I-MIBG and studied its utility in diagnosis of primary and metastatic neural crest tumours. Studies were carried out in 54 patients. Of them 39 cases were of neuroblastomas, 1 pheochromocytoma; 6 operated medullary carcinomas; 5 paragangliomas; 2 Ewing's sarcoma and 1 Rhabdomyosarcoma; The sensitivity for the detection of primary tumours of neuroblastomas was 94% and for the detection of metastasis was 83%; while in the case of paragangliomas and medullary carcinoma, the sensitivity was 75% and 70% respectively. Our experience in the present study shows that 131I-MIBG scintigraphy is a sensitive and specific diagnostic tool to localise primary and metastatic disease of neural crest tumours.

Localization of a pheochromocytoma using I-123 MIBG adrenal scintigraphy.

In a patient with the clinical diagnosis of pheochromocytoma, the localization of the tumor is essential for planning treatment. Recently, we have performed I-123 metaiodobenzylguanidine (MIBG) adrenal scintigraphy in a patient presenting with a history of paroxysmal hypertension. Scintigraphy accurately located an ectopic unilateral pheochromocytoma. The scintigraphic diagnosis was confirmed by surgery and a diagnosis of ectopic unilateral pheochromocytoma was made by histopathological examination. This case report illustrates the specific diagnosis of pheochromocytoma by I-123 MIBG scintigraphy which is especially useful when other diagnostic procedures are equivocal.

The management of Graves' disease by Indian thyroidologists.

BACKGROUND. Although effective modes for treating Graves' disease are available, there is controversy over their choice. We conducted a nation-wide survey to determine trends in the diagnosis and management of Graves' disease in India. METHODS. A proforma was mailed to 45 practising thyroidologists who were members of the Endocrine Society of India or the Thyroid Association of India. One index case and 5 variations were provided, and the members were asked to indicate the investigations of choice, therapeutic modality and details about its implementation. RESULTS. The overall response rate was 71% (32). For diagnosis, serum T3, T4, TSH, sensitive TSH, free T3, and free T4 were asked for by 24, 25, 6, 13, 5, and 10 responders respectively. Radioactive iodine uptake with or without a scan was obtained by 19 of the responders. Antithyroid drugs were the choice of the majority in most situations (index case: 40-year-old female with first episode of typical Graves' disease--23; 40-year-old male--20; 16-year-old male--32; 40-year-old female without goitre--25), except for the patient with relapse and the 65-year-old female where radioiodine was the choice of the majority (20 and 23 respectively). CONCLUSION. Antithyroid drugs are the mainstay of treatment of Graves' disease in India. The predominant use of these drugs was similar to European data, but different from the practice in the USA, where radioiodine is used much more liberally.

Determination of hemoglobin Bart's in alpha thalassemia traits by two-site immunoradiometric assay. I. Purification of hemoglobin Bart's and preparation of specific anti-Hb Bart's.

This research report describes methods for the preparation of hemolysate and the isolation and purification of hemoglobins Bart's, A, A2, E, F and H. Procedures for the preparation of anti-Hb Bart's by injecting purified Hb Bart's into rabbits is indicated in the time schedule. The rabbit antisera were evaluated by antigen-antibody reaction in agar gel. Although the antiserum reacted with Hb Bart's but not with Hb A, A2,E and H, it also cross-reacted with Hb F. After the rabbit antisera were absorbed with Hb F, the antisera were highly specific because it only reacted with Hb Bart's. The purified specific anti-Hb Bart's was labelled with radioactive 125I by chloramine-T method. After passing through Sephadex G-100 column, the 125I labelled specific anti-Hb Bart's was obtained in the first peak. This radioactive labelled anti-Hb Bart's was ready to use in the two-site immunoradiometric assay.

Analysis of 105 uninodular goitres.

Data on 105 solitary thyroid nodules, confirmed at surgery to be solitary, is presented. Six (5.7%) were malignant, 4 papillary and 2 follicular. The sensitivity and the specificity of 131I radionuclide thyroid scan (n = 90) were 100% and 24% respectively. Similarly, the sensitivity and specificity of fine needle aspiration cytology (n = 65) was 75% and 100% respectively. In both instances, the "gold standard" was the histopathology of the surgically removed nodule. In order to avoid unnecessary surgery, without missing malignancy, we would recommend the combination of radionuclide thyroid scan and FNAC for investigation of solitary thyroid nodules.

Thyroid morphometry and intrathyroidal 131-I iodine transit kinetics in Kashmiri population.

Morphometric--kinetic parameters of the thyroid gland in the Kashmiri population, which is geographically, environmentally, socioculturally, anthropologically and ethnically different from that of the main country (Indian republic), have been analysed. Morphometrically, the gland in this population has been found to be significantly larger (p less than 0.001), while kinetically, the A max which is the ordinate-extrapolate of the best-fit RAIU(t) curve, has been found to be significantly lower (p less than 0.01). The majority of other structural and functional parameters were similar to those of the north Indian population.

Altered maternal thyroid function: fetal and neonatal development of rat.

Influence of maternal thyroid status on fetal and neonatal development of rats has been studied. Maternal hypothyroidism resulted impaired reproduction and intrauterine growth retardation of offsprings as revealed by their reduced body weight, heart weight, body length and tail length. Offsprings born to hypothyroid mothers showed very high rate of mortality and none of them survived beyond eight days. Maternal hyperthyroidism did not cause any abnormality on reproduction. Hyperthyroid mothers showed increased rate in body weight gain during pregnancy which was associated with increased weight of body and heart of fetuses born to hyperthyroid mothers. Plasma thyroxine was not measurable in fetus from hypothyroid mothers till 21st day of gestation. The results of the present study showed that maternal thyroid status plays an important role in fetal and neonatal growth and development.

Etiology of childhood hypothyroidism.

This study prospective without any selection bias included 80 of the 152 hypothyroid infants and children seen over the past six years. The clinical diagnosis was confirmed by TSH and thyroid hormone (T3, T4) studies. Scanning for thyroid with TC99m pertechnetate was carried out in all except seven older children with grade II and III goiters where 131I uptake studies were done. Serum thyroglobulin (RIA) was estimated and antithyroglobulin and antimicrosomal antibodies were tested. Based on thyroid 131I scan or 131I uptake, 52.5% had no demonstrable thyroid tissue except one with hypoplasia (Group I, n = 42), 25% had ectopic thyroid (Group II, n = 20), and 22.5% had normal or enlarged thyroid gland (Group III, n = 18). One hypothyroid patient of Group III had thyroiditis with high antibody titre and one was proved to have iodine deficiency). The mean age at time of diagnosis was lowest in Group I (age in months--30.3 +/- 36.2; 60.6 +/- 53.9; 106.2 +/- 69.3 in Groups I, II and III respectively. The intergroup differences in age were significant. The mean serum Tg levels increased progressively from Groups I to III. In the present series thyroid dysgenesis led to hypothyroidism in 77.5%, with athyreosis in 52.5% and ectopia in 25%. Dyshormonogenesis was noted in 20% and thyroiditis in 1.5%.

Comparative analysis of surface components of adult, micro-filariae and infective larvae of Brugia malayi.

A comparative analysis of surface proteins of adult, microfilariae and infective larvae of Brugia malayi, the human filarial parasite, has been carried out using IODOGEN (1,3,4,6-tetrachloro-3,alpha 6 alpha-diphenyl-glycoluril) and lactoperoxidase methods. SDS-polyacrylamide gel electrophoretic and autoradiographic analyses revealed the presence of 9 proteins (15-200 kDa) in adults, while microfilariae and infective larvae showed 8 and 6 proteins (15-120 kDa), respectively. The pattern of proteins radiolabelled by IODOGEN method was very similar to that of proteins labelled by the lactoperoxidase method. Since these proteins are released by the protease treatment of whole parasites, they are likely to be present on the surface of the parasite.